- Scientific understanding of the immune response to COVID-19 is incomplete but numerous research studies are underway.
- There is little evidence to suggest that exposure to other coronaviruses can confer protection against SARS-CoV-2.
- There is very good evidence that it takes at least 14 days to develop an antibody response to SARS-CoV-2.
- A significant proportion of people exposed to SARS-CoV-2 make very little or no detectable antibodies at all.
- There is insufficient scientific evidence to know whether the presence of SARS-CoV-2 antibodies confers protection from subsequent infections, and if so at what level.
- The duration of immunity is not clear; long-term monitoring of this in large studies will be needed to provide clarity.
- Antibodies are only one part of the immune response to infection, which is complex, and understanding the overall immune response to COVID-19 is very important.
- Additional high-quality research evidence is needed in order to indicate the likelihood of future outbreaks of disease, how often and when they are likely to occur, and to inform the development of any future immunisation programmes.
- This is part of our rapid response content on COVID-19. The article will be updated as the research progresses. You can view all our reporting on this topic under COVID-19.
This article gives an overview of the body’s immune response to infection. It explains current understanding of the immune response to SARS-CoV-2, highlighting the latest evidence emerging from research, with a focus on the role of antibodies. This is directly relevant to the development and use of antibody tests, discussed in Antibody tests for COVID-19.
Antibodies and the immune response
The immune system involves complex structures and processes that protect us from disease. It has two main features:
Innate immunity is the first line non-specific defence to infections. This comprises the body’s physical barriers, such as the skin, and the cell linings of internal body parts, such as the airways and lungs. All cells in the body have the capacity to mount or modulate immune responses, through the release of substances, when exposed to pathogens. The innate immune system also has a variety of specialised cells that offer protection in the first days of exposure to a pathogen such as a virus or bacterium.
Adaptive immunity describes how the body builds immunological memory – so that if the person is exposed to the same infection again the body’s response is enhanced. This is the basis for immunisation with vaccines. Key features of this adaptive response are that it is specific for the structures on a specific pathogen and that immune memory facilitates an improved response on subsequent encounters. It involves antibodies that bind specifically to the pathogen, and white blood cells, termed T cells, which kill infected cells. This type of immunity can be strong or weak, short- or long-lived, and this is a complex result of several factors. It can take up to 3 weeks to develop this type of immunity. While adaptive immunity may be complex and multi-faceted, measuring antibodies in blood can be regarded as a good proxy for adaptive immunity.
Antibodies (also called immunoglobulins) are specialised molecules, produced by the immune system to fight infection when the body is exposed to a pathogen. There are different types of antibodies. Some antibodies bind to and neutralise the pathogen, while others activate other parts of the immune system to enhance the body’s response:
- B lymphocytes recognise antigens and make antibodies. Each B cell makes one specific antibody.
- T lymphocytes comprise 2 types: helper T cells that coordinate the immune response, including stimulation of B cells to make more antibodies and to attract killer T cells, which destroy infected cells.
The immune system can differentiate between the body’s own tissue (‘self’) and foreign tissue (‘non-self’) or molecules. It does this by detecting proteins called antigens that are found on non-self cell surfaces or virus particles. The surface of SARS-CoV-2 virus particles are covered with club-shaped spikes of protein, an antigen which is recognised by antibodies. A SARS CoV-2 antibody can lock onto the antigen and signal to other immune cells that then kill it. Some trial vaccines are based on this surface antigen. It plays a key role in the infection pathway of virus, since it enables the virus to attach to and enter human cells. This and other antigens expressed by SARS-CoV-2 are detected by tests.
There are five types of immunoglobulins, made in response to different stages of an infection and expressed in different tissues such as blood, lymph, breast milk or saliva. Current SARS-CoV-2 antibody tests look for IgM, IgA, IgG or some combinations of them. Some tests can quantify the levels, while other only indicate their presence or absence.
Immune response to COVID-19
There is an increasing body of evidence describing the immune response to COVID-19 and the antibodies that are produced. This will inform clinical treatment and vaccine development and testing.
The response to SARS-CoV-2, as with other viruses, involves a complex immunological response as the body tries to counter the virus. Some of the understanding of these processes is informed by research on other coronaviruses. Research has shown that having antibodies is not necessarily protective against repeated infections. A detailed knowledge of the body’s immune response and studying the role that antibodies play is essential, thus accurate antibody tests are an important research tool for studying infections.
Several antibody therapies are in development and being tested in COVID-19 patients. Studies using convalescent plasma donated from patients who have recovered from COVID-19 have shown promising results. A Cochrane review published in May reported that there is limited evidence on the benefits of convalescent plasma, so large well-designed studies are needed to determine any benefits. A UK trial of this treatment for adults with COVID-19 in intensive care is being coordinated by NHS Blood and Transplant.
Duration of immunity
SARS-CoV-2 is a member of a family of coronaviruses. These include viruses that can cause the common cold, and other respiratory illnesses including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). There is insufficient evidence to suggest that exposure to other coronaviruses can confer protection against SARS-CoV-2. Research on other coronaviruses (MERS-CoV and SARS-CoV) has examined how long people had antibodies against these viruses. A review summarising emerging themes from lots of individual studies was published on 20 May. After 2–3 years, most people who had been infected had minimal levels of detectable antibody. People who had had more severe disease had higher levels of antibodies, and they were present for longer. It is currently unclear the degree to which other coronaviruses, such as those that cause the common cold, provide protection against SARS-CoV-2 or interfere with antibody tests.
Many studies of people hospitalised with COVID-19 have looked at the development of antibodies to SARS-CoV-2. An antibody response takes 10–14 days to develop, and at least a component of this is of the useful ‘neutralising’ type (both binds to the virus and stops its activity). A significant subset of people make little or no detectable antibody; this includes those who may have been very mildly affected and may have had little immune stimulation by the virus. There is little evidence on how long these antibodies remain; this is a key focus of current research. This is relevant to the question of how subsequent waves of infection will affect people. Large scale studies that measure antibody status in different groups of people over time (longitudinal studies) are essential – such studies are underway and discussed in Antibody tests for COVID-19. Data from these studies will indicate how likely it is that SARS-CoV-2 becomes a seasonal virus (like influenza) and how frequently mini-epidemics will occur (for example, annually or sporadically). It is also essential for the development of immunisation programmes if a vaccine becomes available.
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